On removal of charge singularity in Poisson-Boltzmann equation.

The Poisson-Boltzmann theory has become widely accepted in modeling electrostatic solvation interactions in biomolecular calculations. However the standard practice of atomic point charges in molecular mechanics force fields introduces singularity into the Poisson-Boltzmann equation. The finite-difference/finite-volume discretization approach to the Poisson-Boltzmann equation alleviates the numerical difficulty associated with the charge singularity but introduces discretization error into the electrostatic potential. Decomposition of the electrostatic potential has been explored to remove the charge singularity explicitly to achieve higher numerical accuracy in the solution of the electrostatic potential. In this study, we propose an efficient method to overcome the charge singularity problem. In our framework, two separate equations for two different potentials in two different regions are solved simultaneously, i.e., the reaction field potential in the solute region and the total potential in the solvent region. The proposed method can be readily implemented with typical finite-difference Poisson-Boltzmann solvers and return the singularity-free reaction field potential with a single run. Test runs on 42 small molecules and 4 large proteins show a very high agreement between the reaction field energies computed by the proposed method and those by the classical finite-difference Poisson-Boltzmann method. It is also interesting to note that the proposed method converges faster than the classical method, though additional time is needed to compute Coulombic potential on the dielectric boundary. The higher precision, accuracy, and efficiency of the proposed method will allow for more robust electrostatic calculations in molecular mechanics simulations of complex biomolecular systems.